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  • Perspective
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Individualized and innovative gender healthcare for transgender and nonbinary youth

Nature Reviews Endocrinology volume 21, pages 441–452 (2025)Cite this article

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Abstract

Increasing numbers of transgender and nonbinary youth are now accessing gender-affirming medical interventions, which have been demonstrated to improve health and well-being. This Perspective addresses how the needs of transgender and nonbinary youth, up to age 18, can be addressed through individualized gender-embodiment care. We first review standard medical therapies, including gonadotropin-releasing hormone analogues, 17β-oestradiol, testosterone, steroidal antiandrogens and progestins, followed by presenting novel approaches to individualizing gender healthcare for transgender and nonbinary youth, consisting of selective oestrogen receptor modulators, 5α-reductase inhibitors, aromatase inhibitors and non-steroidal antiandrogens. Ethical guidance for off-label prescribing is provided, grounded in the principles of evidence, benefit, safety, respect, care, communication, transparency, equity and innovation. These ethical principles are applied in three clinical scenarios in which off-label therapies are considered. We conclude that standard medical therapies are ethically justified and that novel therapies can be ethically acceptable when carefully considered in the context of an individual youth’s care plan and taking into account the available theoretical, clinical and research evidence as well as the potential benefits and potential risks. In keeping with the principle of innovation, we encourage clinicians and researchers to share evidence of medical innovations that support the gender health of transgender and nonbinary youth.

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Acknowledgements

D.B.A.C. (they) and D.L.M. (he) live and work within the traditional, ancestral and unceded territories of the xʷməθkwəýəm (Musqueam), Sḵwx̱wú7mesh Úxwumixw (Squamish) and səlili̓lw̓ətaʔɬ (Tsleil-Waututh) Nations. K.C.P. (he) lives and works on the unceded lands of the Wurrundjeri people of the Kulin nation and wishes to acknowledge funding support from the Australian National Health and Medical Research Council (GNT#2006529 and # 2027186) and the Hugh DT Williamson Foundation. C.S.A. (he/they) lives and works on the traditional lands of the Haudenosaunee Confederacy. K.K. (she) lives and works on unceded Anishinaabe Algonquin territory.

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Authors and Affiliations

  1. School of Nursing, The University of British Columbia, Vancouver, British Columbia, Canada

    Drew B. A. Clark

  2. Provincial Health Services Authority, Vancouver, British Columbia, Canada

    Drew B. A. Clark & Daniel L. Metzger

  3. Department of Paediatrics, The University of British Columbia, Vancouver, British Columbia, Canada

    Daniel L. Metzger

  4. Clinical Sciences Theme, Murdoch Children’s Research Institute, Parkville, Victoria, Australia

    Ken C. Pang

  5. Department of Adolescent Medicine, The Royal Children’s Hospital, Parkville, Victoria, Australia

    Ken C. Pang

  6. Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia

    Ken C. Pang

  7. Riverside Family Medicine, New York, NY, USA

    Colton St. Amand

  8. Department of Paediatrics, University of Ottawa, Ottawa, Ontario, Canada

    Karine Khatchadourian

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K.K. served on advisory boards or as a consultant for Tolmar.

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Clark, D.B.A., Metzger, D.L., Pang, K.C. et al. Individualized and innovative gender healthcare for transgender and nonbinary youth. Nat Rev Endocrinol 21, 441–452 (2025). https://doi.org/10.1038/s41574-025-01113-z

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